Wolfe Laboratory

Welcome to the Wolfe Lab, supervised by John H. Wolfe, Professor of Pathology and Medical Genetics in Pediatrics and Director, Walter Flato Goodman Center for Comparative Medical Genetics.

Description of Research

Our lab works on transferring disease correcting genes into the central nervous system (CNS) in animal models of human genetic diseases. In these diseases, the CNS is often not rescued by the therapies that help the rest of the body. The lab studies both ex vivo gene transfer into neural stem cells that are then transplanted and in vivo transfer using vectors injected directly into the brain.

Our studies involve comparisons of both the vectors used to introduce the genes into cells and the properties of the genes themselves. Additionally, we examine the ability of different cell types and subregions of the brain to be corrected. We also pursue new methods to follow the corrected cells and the expression of the correcting gene in the live animal using MRI and PET techniques. For a complete understanding of the therapy, we also are working on achieving a better understanding of the mechanism of these diseases in the brain.

Projects

Projects involve the molecular design and engineering of vectors, the understanding of the fate of vector-transferred genes in the brain, the regulation of gene expression from vectors, the biology of neural stem cell, the study of induced pluripotent stem cells (iPS), the use of imaging studies in genetic disease and gene therapy, and the proteomic and genomics analysis of the neurodegenerative brain. For students, projects can be tailored to interests, learning goals, and experience.

Contact Information

John H. Wolfe, PhD

Professor, Pathology and Medical Genetics, School of Veterinary Medicine and Department of Pediatrics, School of Medicine

Dr. Siddiqi's research interests are focused on understanding the molecular underpinnings of inherited neurodegenerative diseases, stem cell biology and CNS transplantation therapy. He has employed neurodevelopmental models to better appreciate endogenous stem cell diversity and subsequent lineage production that may become dysfunctional in the developed brain. His translational research goals concentrate on modifying immortalized and iPSC-derived neural stem cells with genetic factors to facilitate engraftment into the diseased brain. He utilizes a combination of cell culture techniques, genetic fate mapping, bioinformatics analysis, live-cell confocal imaging and transgenic animal studies with in vivo transplantation in these studies.

Lucia Mayela Gayosso Miranda, PhD

Post-doctoral Fellow

Contact: gayossoL@email.chop.edu

Jacqueline Hunter, PhD

Post-doctoral Fellow

Dr. Hunter is a postdoctoral fellow in the Wolfe Laboratory. She received her PhD in Pharmacology & Toxicology from the University of the Sciences in Philadelphia. Her research focuses on evaluating the therapeutic efficacy of viral vector-mediated gene delivery to the brain using feline models of lysosomal storage disorders.

Margaret Lippincott

Research Technician

email: lippincotm@email.chop.edu

Ms. Lippincott's work and experience involves maintaining the animal colony, including weaning, breeding, and managing rodent colony population. Also, she works on genotyping and assisting with other tasks in the lab.